Chronic Obstructive Pulmonary Disease (“COPD”) is a chronic disease of the lungs, in which the fine inner structure of the lungs is destroyed over time, creating large voids within the lung, leading to trapping of inhaled air and loss of lung elasticity (hyperinflation). Common symptoms of COPD (which includes chronic bronchitis and emphysema) are shortness of breath, excessive production of sputum, and chronic cough. Persons suffering from COPD may also experience frequent and sudden worsening of symptoms (exacerbations).
COPD is characterized by pathological changes in the lungs and airways, as prolonged irritation leads to chronic inflammation that often persists even after the source of irritation (e.g., tobacco smoke) is no longer present. COPD is progressive and ultimately life-threatening disorder. Treatment can slow its progression; there is currently no cure.
Most risk factors for COPD are environmental. The most common cause of COPD is exposure to tobacco smoke, including second-hand (passive) smoking. Exposure to indoor and outdoor air pollution, or occupational exposure to dust, particulates, or toxic vapors or fumes can also cause COPD. Frequent lower respiratory tract infections during childhood can also increase susceptibility to COPD.
Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD), including emphysema, call for immediate reduction of patient exposure to risk factors. Risk factors include tobacco smoking and occupational or environmental exposure to particulates or harmful gases. Smoking cessation may be accomplished through patient education and counseling; pharmacotherapeutic intervention may also be effective.
As COPD progresses, medical therapy may be initiated. The standard of care for treatment of stable Stage II (Moderate) and Stage III (Severe) COPD consists of treatment with one or more bronchodilators, including β2 agonists, anticholinergic drugs, and methylxanthines administered orally or inhaled via nebulizer. However, there is no evidence that bronchodilators are capable of significantly improving FEV1 or arresting or slowing the inexorable decline in lung function in emphysematous patients. Thus, medical therapy for COPD is primarily used for symptomatic relief, to prevent complications, to increase exercise tolerance, and to treat exacerbations of COPD.
Treatment with inhaled glucocorticosteroids, alone or in combination with bronchodilator therapy, can reduce the frequency of exacerbations and may be indicated in patients with Severe or Very Severe COPD, but is not recommended for patients with mild or moderate COPD as long-term treatment with glucocorticosteroids is associated with steroid myopathy.
Pulmonary rehabilitation, consisting of exercise training programs, nutrition counseling, and patient education are used to treat symptoms of COPD and to improve the patient's overall quality of life, particularly among patients with Stage II (Moderate), Stage III (Severe) and Stage IV (Very Severe) COPD.
Long-term (>15 hours/day) therapy with oxygen (O2) increases survival in patients with COPD and has been shown to improve hemodynamics, exercise tolerance, lung mechanics, and can ameliorate mental deficits incurred through COPD-induced hypoxemia. Patients with COPD receive benefit from long-term oxygen therapy primarily through increased oxygen saturation.
Lung volume reduction surgery (LVRS), in which tissue from one or both lungs is resected in order to treat the physiological consequences of emphysema (enlargement of air spaces, destruction of diffusive capacity, decrease in elastic recoil with consequent reduction in expiratory airflow, hyperinflation, and trapping of air), was first conducted in human subjects in 1957 by Brantigan and Mueller. However, despite patient-reported symptomatic improvement, a high operative mortality rate (18%) precluded its acceptance as a treatment for COPD.
More recently, a series of clinical studies in patients with COPD, including prospective randomized trials, showed that LVRS resulted in benefit for lung function, gas exchange, and quality of life (QOL) measures. The National Emphysema Treatment Trial (NETT) randomly assigned 1218 subjects with severe emphysema to receive pulmonary rehabilitation with or without LVRS. Study results showed statistically significant improvement in exercise capacity among patients receiving both medical therapy and LVRS (15% vs. 3%; P<0.001) and a prespecified subgroup analysis showed a survival advantage at 24 months for patients with predominately upper-lobe emphysema and low baseline exercise capacity who were considered to be at high risk for death from surgery. However, subgroup analysis also suggested that high-risk patients with upper-lobe disease and high initial exercise capacity were poor candidates for LVRS due to increased mortality and lack of significant benefit.
Long-term follow-up of NETT subjects showed a survival benefit for patients assigned to LVRS plus medical therapy overall, as well as lasting improvement in exercise capacity and health-related QOL relative to the medical-therapy-only group. The subgroup of high-risk/high exercise capacity subjects receiving LVRS showed no survival benefit but demonstrated improved exercise capacity.
On the basis of these results, LVRS has been recommended as a palliative treatment for emphysema for the aforementioned sub-groups of patients. LVRS for the treatment of emphysema is also a costly procedure relative to standard medical therapy, and until more data are available, the cost-effectiveness of the procedure remains unclear.
Pharmacological approaches to treating emphysema patients have not yielded significant improvements in large randomized studies. Although LVRS has efficacy benefits, the high mortality and morbidity rates results in high costs. Therefore, minimally invasive approaches (such as bronchoscopic LVR) that decrease mortality and morbidity while offering significant efficacy are desired.
Several bronchoscopic LVR approaches (including plugs, valves and stents) are currently under investigation. Most bronchoscopic approaches involve the blocking or occluding of major airways that supply emphysematous regions of the lung. Bronchoscopic LVR achieved through implantation of one-way endobronchial valves has been explored in human subjects in single-center pilot studies and in larger multicenter studies. In this procedure, one-way endobronchial valves are delivered bronchoscopically to the airway of the emphysematous lung region(s). The goal of the valve is to create collapse or atelectasis of the region of the lung similar to that achieved by LVRS. Initial multicenter experience with endobronchial valves suggests that the therapy is well tolerated, with a 90-day mortality of 1.02%, compared to 7.9% reported for the NETT LVRS study. A total of 53 patients out of 98 (54%) did not demonstrate clinically significant improvement in FEV1 at 90 days, and only 23% showed improvement in exercise tolerance. This lack of improvement is likely attributable to collateral ventilation, which precludes lobar collapse despite occlusion of the major airways.
A bronchoscopic approach that creates consistent LVR despite the presence of collateral ventilation is desired. An approach is also desired that can be tailored, if need be, to safely and effectively treat any patient.
In addition to treating LVR, an approach is also desired that can treat a variety of other lung conditions, such as lung tumors, nodules, infiltrates, bacteria, fungi, viruses and other diseases and conditions.